INTRODUCTION. The impact of several environmental and genetic factors on diabetes mellitus and its complications is well documented. It has also been established that cytokines play key roles in the pathogenesis of nephropathy. Polymorphisms of the -590 region of interleukin (IL)-4 are associated with the regulation of expression of this gene. In this study, we aimed to find polymorphisms of this region in nephropathic type 2 diabetic patients. MATERIALS AND METHODS. Peripheral blood samples were collected from 100 type 2 diabetic patients with nephropathy and 150 healthy controls. DNA was extracted and a polymerase chain reaction-restricted fragment length polymorphism technique was performed to examine polymorphisms in the -590 region of the IL-4 gene. RESULTS. Our results showed a significant difference between the C/C, T/C, and T/T genotypes and the C and T alleles of the -590 region of IL-4 in nephropathic patients in comparison with the healthy controls. CONCLUSIONS. Results of this study suggest that the functional gene polymorphisms of IL-4 play an important role in the pathogenesis of diabetic nephropathy in patients with type 2 diabetes mellitus.